Mucositis, Pain, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
mucositis, unspecified adult solid tumor, protocol specific, pain
Brief summary
This was an open-label, single-dose study to assess the safety, tolerability, and absorption/distribution kinetics of a single 100 µg dose of fentanyl sublingual spray in opioid-tolerant cancer subjects, with or without oral mucositis.
Detailed description
RATIONALE: One dose of fentanyl sublingual spray may be effective in relieving pain in opioid-tolerant cancer patients. PURPOSE: This phase III trial is studying the side effects of fentanyl sublingual spray and to see how well it works in treating opioid-tolerant cancer patients with or without oral mucositis. OBJECTIVES: Primary * To compare the absorption/distribution kinetics of a single dose of fentanyl sublingual spray in opioid-tolerant cancer patients with or without oral mucositis. * To evaluate the safety and tolerability of this regimen. OUTLINE: This is a multicenter study. Patients fast for at least 8 hours before and at least 4 hours after and no water is allowed for at least 1 hour before and at least 1 hour after study drug administration. Patients receive a single dose of fentanyl sublingual spray while in an upright position in clinical care recliners or beds, and remain in an upright posture for at least 4 hours after administration. Patients are instructed not to swallow for at least 5 minutes after administration and not to expectorate the drug. After study drug administration, 10 blood samples are collected over a 12-hour period for pharmacokinetic and other analyses.
Interventions
Fentanyl was supplied in single-dose glass vials assembled into a delivery device to be used as a sublingual spray.
Sponsors
INSYS Therapeutics Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of cancer and meets 1 of the following criteria: * Mild mucositis, defined as grade 1 (erythema of the mucosa) or 2 (patchy ulcerations or pseudomembranes) on the day of study drug administration. * No mucositis, defined as normal oral cavity upon examination on the day of study drug administration. * Opioid-tolerant, defined as patients who are taking ≥ 60 mg of oral morphine/day, ≥ 30 mg of oxycodone/day, ≥ 8 mg of oral hydromorphone/day, or an equianalgesic dose of another opioid for ≥ 7 days for cancer-related pain. * Persistent pain related to cancer or its treatment over the past 7 days. * No brain metastases with signs or symptoms of increased intracranial pressure. PATIENT CHARACTERISTICS: * Negative pregnancy test. * Agree to be confined to study site for approximately 12 hours, to eat only the food served by the study unit during the study confinement period, and to consume all food provided at the designated meal or snack times. * No history of major organ system impairment or disease that, in the investigator's or his/her designee's opinion, could increase the risk associated with the use of opioids. * No uncontrolled hypertension despite antihypertensive therapy or history of hypertensive crisis within the past 2 years. * No recent history (within the past 2 years) of transient ischemic attacks, neural vascular disease, stroke, or cerebral aneurysms. * No intolerable side effects to opioids or fentanyl. PRIOR CONCURRENT THERAPY: * See Disease Characteristics. * More than 30 days since prior investigational agents. * More than 14 days since prior monoamine oxidase inhibitors. * No prior participation in either Insys Fentanyl Sublingual Spray Phase III study INSYS-INS-05-001 or INSYS-INS-06-007. * No other concurrent use of any fentanyl product. * Patients who have received Actiq®, Fentora®, or Duragesic® are eligible after a 7-day washout. * No concurrent medications (prescription, over-the-counter, vitamin, or herbal substances) except for hormonal contraceptives and/or ≤ 3 doses of acetaminophen at ≤ 1 g each.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Fentanyl | Pre-dose to 12 hours post-dose | Cmax is defined as the maximum drug concentration in plasma and was determined from individual plasma concentration versus time data. Blood samples for pharmacokinetic analysis were drawn pre-dose; 15 and 30 minutes; and 1, 2, 4, 6, 8, 10, and 12 hours post-dose. Fentanyl concentration assays were performed using a fully validated and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results are reported for patients with and without mucositis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax of Fentanyl | Pre-dose to 12 hours post-dose | Tmax is defined as the time to reach the maximum concentration of fentanyl in plasma and was determined from individual concentration versus time data. Blood samples for pharmacokinetic analysis were drawn pre-dose; and 15 and 30 minutes; and 1, 2, 4, 6, 8, 10, and 12 hours post-dose. Fentanyl concentration assays were performed using a fully validated and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results are reported for patients with and without mucositis. |
| AUC0-last of Fentanyl | Pre-dose to 12 hours post-dose | AUC0-last is defined as the area under the plasma concentration-time curve from time-zero to the time of the last quantifiable concentration of fentanyl, was calculated using the linear trapezoidal rule, and was determined from individual concentration versus time data. Blood samples for pharmacokinetic analysis were drawn pre-dose; and 15 and 30 minutes; and 1, 2, 4, 6, 8, 10, and 12 hours post-dose. Fentanyl concentration assays were performed using a fully validated and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results are reported for patients with and without mucositis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fentanyl Sublingual Spray 100 µg Participants received a single administration of fentanyl sublingual spray 100 µg sublingually. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Fentanyl Sublingual Spray 100 µg |
|---|---|
| Age Continuous | 46.6 years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 |
Outcome results
Primary
Cmax of Fentanyl
Cmax is defined as the maximum drug concentration in plasma and was determined from individual plasma concentration versus time data. Blood samples for pharmacokinetic analysis were drawn pre-dose; 15 and 30 minutes; and 1, 2, 4, 6, 8, 10, and 12 hours post-dose. Fentanyl concentration assays were performed using a fully validated and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results are reported for patients with and without mucositis.
Time frame: Pre-dose to 12 hours post-dose
Population: Pharmacokinetic (PK) population: All subjects who had evaluable plasma profiles to calculate reliable estimates of PK parameters and who had no major protocol deviations. One subject in the non-mucositis group self-administered a fentanyl product before receiving the study drug and was excluded from the PK population due to this protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fentanyl Sublingual Spray 100 µg - Mucositis | Cmax of Fentanyl | 0.67 ng/mL | Standard Deviation 0.6 |
| Fentanyl Sublingual Spray 100 µg - Non-mucositis | Cmax of Fentanyl | 0.26 ng/mL | Standard Deviation 0.15 |
Secondary
AUC0-last of Fentanyl
AUC0-last is defined as the area under the plasma concentration-time curve from time-zero to the time of the last quantifiable concentration of fentanyl, was calculated using the linear trapezoidal rule, and was determined from individual concentration versus time data. Blood samples for pharmacokinetic analysis were drawn pre-dose; and 15 and 30 minutes; and 1, 2, 4, 6, 8, 10, and 12 hours post-dose. Fentanyl concentration assays were performed using a fully validated and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results are reported for patients with and without mucositis.
Time frame: Pre-dose to 12 hours post-dose
Population: Pharmacokinetic evaluable population: All subjects who had evaluable plasma profiles to calculate reliable estimates of pharmacokinetic parameters and who had no major protocol deviations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fentanyl Sublingual Spray 100 µg - Mucositis | AUC0-last of Fentanyl | 3.11 hr*ng/mL | Standard Deviation 4.8 |
| Fentanyl Sublingual Spray 100 µg - Non-mucositis | AUC0-last of Fentanyl | 0.91 hr*ng/mL | Standard Deviation 0.13 |
Secondary
Tmax of Fentanyl
Tmax is defined as the time to reach the maximum concentration of fentanyl in plasma and was determined from individual concentration versus time data. Blood samples for pharmacokinetic analysis were drawn pre-dose; and 15 and 30 minutes; and 1, 2, 4, 6, 8, 10, and 12 hours post-dose. Fentanyl concentration assays were performed using a fully validated and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results are reported for patients with and without mucositis.
Time frame: Pre-dose to 12 hours post-dose
Population: Pharmacokinetic (PK) population: All subjects who had evaluable plasma profiles to calculate reliable estimates of PK parameters and who had no major protocol deviations. One subject in the non-mucositis group self-administered a fentanyl product before receiving the study drug and was excluded from the PK population due to this protocol deviation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fentanyl Sublingual Spray 100 µg - Mucositis | Tmax of Fentanyl | 0.53 hr | Standard Deviation 0.57 |
| Fentanyl Sublingual Spray 100 µg - Non-mucositis | Tmax of Fentanyl | 0.56 hr | Standard Deviation 0.59 |